PB2525: A FOUR YEARS’ EXPERIENCE OF UNIVERSAL NEWBORN SCREENING FOR HAEMOGLOBIN DISORDERS IN UDINE, FVG, NORTHERN ITALY
Authors: Sara Cmet, Anna Rosa Cussigh, Elisabetta Fontanini, Annalisa Lo Sasso, Carmela Santelia, Paola Freschi, Ilaria Liguoro
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) and thalassemia are severe genetic disorders impairing haemoglobin (Hb) function and production, resulting in significant morbidity and mortality, even in the first years of life. A recent increase in the number of people with Hb disorders (HD) has been registered in Europe due to the globalization and migration phenomena. The early detection of HD allows counselling for family members about disease management, prevention of complications and future reproductive decisions. Newborn screening (NBS) programs for HD are now recommended in the United States and Europe, although widespread implementation still needs to be achieved. Moreover, most NBS are based only on High Performance Liquid Chromatography (HPLC) method, with a clear separation and quantification of Hb fractions, and limited to at risk population. Testing with HPLC is a well-known feasible approach, but not so accurate for diagnosis, as it requires to be completed by molecular DNA confirmation analysis. This sequential workflow, in which only one gene is investigated at a time, may be time-consuming and costly, and may miss some rare causative variants, resulting in a delay in genetic counseling and unresolved cases. Next-generation sequencing (NGS) has been also recently reported as an effective method in screening HD and Hb-associated variations to facilitate diagnosis. Aims: The aim of the present study was to assess the feasibility and efficacy of a universal NBS program based on both HPLC and NGS methods, and to estimate the incidence of HD in the area of Udine (North-Eastern Italy). Methods: A public universal NBS for HD started in 2018 at the Hospital of Udine. Parents of all newborns were offered to participate to this program, and infants’ blood samples were collected 2 days after birth or at 37 gestational weeks in preterm infants. HPLC was performed as the first test on samples, then molecular analysis of the beta-globin gene completed the Hb genotype. Results: From July 2018 to December 2022 there were 7396 newborns at Udine’s Hospital. A total of 6980 neonates (94%) were tested for HD. During this period, 101 samples (1.45%) resulted positive for any Hb abnormality, in particular 1 SCD (0.014%),1 β-Thalassemia Major (0.014%), 3 HbCC (0.042%), 66 infants (0.94%) with sickle-cell trait (1 presented an S/G-Philadelphia phenotype) and 15 (0.21%) HbC carriers. Other minor Hb variants were also identified: 11 (0.16%) carriers of HbE, 2 (0.03%) HbD-Punjab, 1 (0.014%) HbG and 1 (0.014%) HbK Woolwich. Children with SCD and β-Thalassemia were immediately redirected from Neonatology to Pediatric Department for the subsequent clinical management and follow-up. All other families of Hb variant positive newborns received genetic counseling. Summary/Conclusion: This study demonstrates the feasibility of a universal NBS program for HD, giving also important information on SCD and thalassemia epidemiology in a Northern Italian area. Based on our results, universal NBS for HD appears to be useful also in a non–endemic area, supporting previous European recommendation for a universal screening. Overall, NGS has an added value in large-scale high throughput carrier screening and in the complex cases for which common molecular techniques have some inadequacies. Therefore, early detection and immediate treatment of affected newborns thanks to molecular analysis techniques may compensate the initial costs of a direct molecular approach. Keywords: Hemoglobin variants, Hemoglobinopathy, Neonate, Sickle cell disease